It is known that a variety of molecular species stimulate the production of antibodies in animals and are thus considered to be immunogenic or antigenic. These molecular species are mostly proteins. It is further known that antibodies may be produced in animals against non-antigenic molecules by the conjugation of those molecules with a known immunogen and vaccinating the animals with the immunogenic conjugate so formed. This immunogenicity of a molecular species may be enhanced by the simultaneous administration of an immunoadjuvant i.e. a material which while not being immunogenic itself potentiates or enhances the animals immune response to the challenging immunogen.
In the art of animal vaccination a subject of continuing interest is the identification of substances that are immuno-adjuvants, and while many such substances, both organic and inorganic, are known, the operative mechanisms involved frequently are only poorly understood.
The continuing wide interest in the discovery of effective immunoadjuvants lies partly in the traditional objective of improving the immunological properties of vaccines that provide protective immunity of animals against pathogenic organisms. A newly emerging objective lies in the perception that novel endocrine-directed vaccines have the potential to directly enhance the productivity of livestock by mechanisms that are entirely unrelated to health maintenance In this field researchers aim to manipulate animal physiology by conferring selected and controlled hormone-specific autoimmunity so that hormonal mechanisms that inhibit productivity can be suppressed. This new field, that could be described as that of "hormonal autoimmunity", differs from classical vaccinations to achieve protective immunity, in that the immunological objective is to achieve effective autoimmunity against specific hormones expressing a limited range of epitopes or even a single epitope. The antigens of this newer field are thus hormones or structural elements of hormones.
Compared to the vast amount of prior art in the field of vaccines for protective immunity the prior art in the field of "hormone-specific autoimmunity" is relatively small. While the present invention is not limited to the field of hormone autoimmunity it nevertheless is of particular relevance to that field of vaccine research.
A common reference immunoadjuvant standard in this field is Freund's Complete Adjuvant (FCA), which comprises a suspension of heat killed M.tuberculosis mycobacteria in mineral oil containing surfactant. Although generally recognised as one of the most powerful immunoadjuvants presently available, FCA has not found wide application outside the laboratory because of the adverse tissue reaction it provokes in recipient animals. FCA is inclined to induce the production of granulomateous lesions in animals at the site of the immunisation. It has also been found that cattle that have been injected with FCA test positive for tuberculosis, when, in fact they may never have been invaded by live and hence infectious M.tuberculosis organisms. It is thus of considerable commercial importance to discover safe effective alternatives.
Two immunoadjuvants known in the art are: (1) mineral oils and vegetable oils, used in conjunction with emulsifiers but without added mycobacteria and (2) the water-soluble polycationic polyelectrolytes such as diethylaminoethyl dextran (DEAE-dextran). The immunoadjuvant oils have immunostimulatory characteristics that are distinct and recognizably different from those of the water soluble polycationic immunoadjuvants. For example, when animals are treated with vaccines formulated into emulsions with oily mycobacteria-free immunoadjuvants, there is a pattern of weak secondary antibody response peaking commonly at 10-20% of that attainable with FCA, but which may nevertheless persist for several months. On the other hand the water-soluble polycationic polyelectrolytes can, under the most favourable circumstances, provoke strong secondary antibody responses, of the order of that when FCA is used, but the responses decline rapidly from peak values.
Those familiar with the art will recognise that these foregoing comparisons with FCA are descriptive of the general kinds of effects that are obtained with mineral oil emulsion adjuvants on one hand and water soluble polyelectrolyte adjuvants on the other. They are clearly not intended to quantify all possible comparisons of this kind in relation to FCA because, in practice, many factors other than the nature of the component immunoadjuvant in a vaccine influence the pattern of the antibody response to vaccination.
Nevertheless while the two important classes of immunoadjuvants that have been described above can usefully enhance immune antibody responses, the value of each class has been limited by the aforesaid characteristics, and the art has lacked an immunoadjuvant which can initially provoke a strong response and yet sustain something more than a modest response for an extended period.